Journal of Blood Medicine最新文献

Background: Iron deficiency anemia is a public health concern among children under five years old. This study aimed to determine the prevalence and determinants of iron deficiency anemia among children under five years attending Luwero General Hospital, Luwero District.

Patients and methods: This cross-sectional study included 380 children under five years old who attended Luweero Hospital. Participants were selected using a simple random sampling technique, and caregivers were interviewed using a structured questionnaire to collect demographic information. Laboratory tests performed were; hemoglobin and ferritin level, to evaluate anemia severity. Iron deficiency anemia was defined as serum ferritin levels below 12 μg/L. Association between determinants and iron deficiency was attained by developing bivariate and multivariate logistic regression models using STATA software version 14, and a p value of <0.05 was considered significant.

Results: This study found that anemia was prevalent amongst children under five years, affecting 38.4% (n = 146) of the sample, with iron deficiency anemia (IDA) identified in 16.6% (n = 63). Majority of the children with iron deficiency anemia had moderate anemia 32 (50.8%). At multivariate analysis, several factors were independently associated with iron deficiency anemia (IDA); male gender (aOR: 2.29, 95% CI: 1.20-4.35, p = 0.012), and children that had infection in the past 3 months (aOR: 5.62, 95% CI: 2.94-10.74, p < 0.000). However, parental age of 20-29 years (aOR: 0.21, 95% CI: 0.06-0.73, p = 0.014) and 30-39 years (aOR: 0.17; 95% CI: 0.05-0.59; p = 0.005) were independently associated with a significantly reduced odds of iron deficiency anemia (IDA).

Conclusion: The study highlights that iron deficiency anaemia is a significant health concern affecting 16.6% of the children studied. Male sex and a recent history of infection were found to be significant independent risk factors for IDA. Conversely, parental age between 20 and 39 years was identified as a strong independent protective factor, with the most pronounced reduction in IDA odds observed among children of parents aged 30-39. Anemia screening and intervention programs should be proactively targeted towards male children, especially those with a recent history of infection.

Erdheim-Chester Disease (ECD) is a rare histiocytic neoplasm characterized by multi-organ tissue infiltration by histiocytes. Clinical presentation and course can be heterogeneous, ranging from localized and asymptomatic bone lesions to a multisystem disease involving skin, cardiac, pulmonary, retroperitoneum, lymph node and central nervous system (CNS) with significant morbidity and mortality. Herein, we describe a rare case of a 61-year-old female patient with ECD with primarily brain and bone involvement who developed "progressive disease" in the CNS after 3 cycles of cladribine. The patient elected to forego any further treatment based on her clinical stability despite progressive disease imaging findings. Subsequent imaging while off treatment demonstrated marked interval improvement in the previously patchy areas of involvement and the patient has continued to have clinical stability 4 years after stopping therapy. The patient was deemed to have experienced pseudoprogression. Pseudoprogression of ECD has not been reported in the literature, and it may be associated with localized inflammatory cytokine release in response to treatment. The possibility of pseudoprogression needs to be considered in evaluating therapeutic response in ECD patients.

Paroxysmal Nocturnal Hemoglobinuria (PNH) is a rare hematologic disorder characterized by intravascular hemolysis through complement activation, bone marrow failure, and thrombosis. The advancement of complement biology has enabled better therapeutic approaches that lead to better clinical outcomes in patients with PNH and other complement-driven hemolytic disorders. The terminal complement inhibitor, eculizumab, was the initial drug available which significantly reduced hemolysis and thrombotic events but failed to resolve residual extravascular hemolysis and transfusion requirements. New therapeutic agents which target proximal complement factors C3, factor B and factor D demonstrate better control of intra- and extravascular hemolysis while decreasing transfusion requirements and improving patient quality of life. This review highlights the evolving therapeutic landscape in complement inhibition by summarizing clinical evidence for the terminal complement inhibitors, as well as pegcetacoplan, iptacopan, and danicopan as emerging agents for treatment of PNH and autoimmune hemolytic anemias-warm AIHA and cold agglutinin disease (CAD). The review also examines ongoing clinical trials and proposes future directions to optimize therapeutic outcomes to address remaining clinical challenges.

Background: Diffuse large B-cell lymphoma (DLBCL) is the most prevalent form of non-Hodgkin's lymphoma globally. SPAG5, a mitotic spindle protein, plays a significant role in DLBCL, where its abnormal expression is often associated with tumor growth, chemotherapy resistance, local recurrence, and poor prognosis.

Methods: A comprehensive analysis of SPAG5 expression across various cancer types was conducted using Timer 2.0 and Sanger Box 3.0. Subsequently, the expression levels of SPAG5 in DLBCL were investigated in comparison to normal samples. Receiver operating characteristic (ROC) curve was then generated to evaluate the diagnostic performance of SPAG5 for DLBCL. Furthermore, the functional role of SPAG5 was characterized, and its impact on the immune microenvironment of DLBCL patients was analyzed. Its potential in predicting immune checkpoint status and responses to immunotherapy was also evaluated.

Results: SPAG5 expression demonstrated significant heterogeneity across various cancer types, with a marked upregulation in DLBCL. The diagnostic efficacy of SPAG5 was moderate, yielding an area under curve (AUC) of 0.75. SPAG5 exerted a multifaceted influence on DLBCL progression by regulating critical cellular processes, including cell cycle dynamics, chromosomal segregation, and DNA homeostasis. Notably, patients with elevated SPAG5 expression had poorer survival outcomes than those with low expression. Analysis of the tumor immune microenvironment revealed a distinct pattern: high SPAG5 expression correlated with increased infiltration of resting natural killer (NK) cells, while being associated with reduced presence of regulatory T cells (Tregs) and follicular helper T cells (Tfh).

Conclusion: Our bioinformatics study elucidated the expression profile, diagnostic potential, and prognostic significance of SPAG5 in DLBCL, emphasizing the complex interplay between SPAG5 expression and the tumor immune landscape. Our findings suggested SPAG5 could be a candidate prognostic marker and potential therapeutic target for DLBCL.

Purpose: To investigate the distribution of antigen and allele frequencies of the MNS blood group system among multi-ethnic populations in East China, and to analyze the genetic polymorphism of uncommon phenotypes, thereby contributing to the enhancement of the regional blood type database.

Patients and methods: A total of 8606 whole blood samples were randomly collected from voluntary blood donors in East China between October 2023 and June 2024. MNS blood group phenotypes were identified using serological methods, and allele frequencies were analyzed and compared across populations. Genetic sequencing was performed on samples with uncommon MNS phenotypes.

Results: The study primarily included the Han, Hui, and Manchu populations. Among the Han population, the most prevalent phenotypes were M+N+S-s+ (45.21%), M-N+S-s+ (25.94%), and M+N-S-s+ (19.84%), respectively. Phenotypic distributions in most other ethnic groups were comparable to that of the Han population, except for the Yi population, which showed a significantly different distribution (P < 0.05). Furthermore, a rare serological phenotype, S-s-, was identified with a frequency of 0.01%. The allele frequencies of the MNS blood group system among different population in East China were consistent with the Hardy-Weinberg equilibrium (P > 0.05).

Conclusion: The MNS blood group system in East China's multi-ethnic populations exhibits polymorphism and regional specificity. Notable allele frequency differences exist between certain minority populations and the Han population. Therefore, it is essential to enhance the development of a regional blood type database tailored to East China in order to support precise clinical transfusion with robust data, including informed pre-transfusion antibody screening for high-risk groups.

Purpose: This study determined the prevalence, types of red cell alloantibodies and factors associated with red cell alloimmunization among transfused patients with CKD at Mbarara Regional Referral Hospital.

Patients and methods: A cross-sectional study was conducted among 141 consented, transfused patients with CKD from March to May 2025. Sociodemographic characteristics and clinical data were collected using a structured questionnaire. Four millilitres of EDTA anticoagulated blood were collected and tested for ABO/Rh blood group, direct antihuman globulin test, and red cell alloantibodies screening and identification by using the Echo Lumena machine (Immucor USA). Data were analyzed using STATA version 17. Logistic regression was used to determine factors associated with alloimmunization, and a p-value of ≤0.05 was considered statistically significant.

Results: Out of 141 patients with CKD, 97 (67.8%) were male, and the mean age was 54.4 ± 17.12. The overall prevalence of red cell alloimmunization was 10 (7.1%). A total of 4 study patients were alloimmunized with a single type of antibody; 2 had multiple antibodies, while 4 had undetermined types. Anti-K was the commonest identified alloantibody. Blood group A had significantly lower odds of alloimmunization (aOR 0.01, 95% CI: 0.0005-0.229, p = 0.004), similar to blood group O (aOR 0.01, 95% CI: 0.0007-0.163, p = 0.001).

Conclusion: The study reveals a slightly higher prevalence of red cell alloimmunization compared to global prevalence, with Anti-K being the most frequent antibody. Only ABO blood group was significantly associated with red cell alloimmunization. Therefore, more studies are needed to evaluate the complex nature of this phenomenon.

Purpose: A central role for the pro-coagulant membrane comprising aminophospholipids (aPL) and enzymatically oxidized phospholipids (eoxPL) in promoting hemostasis via interaction with coagulation factor Gla domains is well established. However, little is known about their interactions with the fibrinolytic pathway, their ability to alter clot structure or to support the activated protein C (APC) pathway. Previous studies used membrane liposome compositions that differ from those expected physiologically and/or generated inconsistent findings. To address this, pro-coagulant membranes comprising physiological proportions of aPL and eoxPL will be tested for their ability to support fibrinolysis using standard assays.

Methods: The impact of phospholipids on clot structure and clot lysis was tested using absorbance-based assays. To investigate the impact of PS or eoxPL on fibrinolysis, plasmin was monitored chromogenically, and clot dissolution measured in a purified lysis system activated by tissue plasminogen activator or urokinase. To determine the impact of eoxPL on APC/protein S, FVa was incubated with APC (± protein S) in a purified prothrombinase assay.

Results: At the concentrations of lipids tested in our study, PS did not significantly impact clot structure or fibrinolysis. Similarly, eoxPL did not impact either fibrinolysis or activity of APC/Protein S.

Conclusion: Using liposome compositions that approximate activated blood cells, we found that the pro-coagulant membrane is unlikely to influence either clot structure or fibrinolytic activity directly, beyond its well characterized role in supporting Gla dependent coagulation factors and the actions of platelet associated proteins/receptors.

Sickle cell disease (SCD) is an inherited haemoglobinopathy caused by a point mutation in the β-globin gene, resulting in abnormal sickle haemoglobin (HbS) and variable clinical expression ranging from mild to severe. While individuals with sickle cell trait are usually asymptomatic, those with homozygous disease may experience chronic haemolytic anaemia, recurrent vaso-occlusive crises, and progressive organ injury. Current standards of care, including hydroxyurea therapy, chronic blood transfusions, and allogeneic haematopoietic stem cell transplantation (HSCT), have substantially improved survival and reduced complications. However, each approach has limitations, such as incomplete disease control, toxicity, and limited donor availability. Recent advances in non-myeloablative and haploidentical HSCT have expanded curative options, achieving high survival with minimal graft-versus-host disease, though accessibility and cost remain challenges. Emerging gene therapies, particularly lentiviral vector-mediated gene addition and CRISPR-Cas9 genome editing, represent major progress by directly targeting the underlying genetic defect. These autologous approaches eliminate donor-related immune risks and have demonstrated durable haemoglobin correction, near-complete resolution of vaso-occlusive events, and encouraging outcomes in stroke prevention. This review synthesises evidence comparing gene therapies with standard treatments, outlining molecular mechanisms, efficacy, safety, and long-term considerations. Key challenges include stem-cell mobilisation, fertility preservation, conditioning toxicity, and equitable access. Early trials show substantial clinical benefit, improved quality of life, and favourable safety profiles. Emerging in vivo editing technologies may further simplify delivery and enhance global accessibility. Integrating gene therapy into evolving standards of care could transform SCD management, offering realistic prospects for durable remission or cure.

Background: The dynamic changes of the hematopoietic system during fetal development may be disrupted by preterm birth. Hematopoietic stem and progenitor cell (CD34⁺) levels are poorly investigated in preterm infants, particularly in relation to immune responses and morbidities. This is partly because of low blood volumes, which raise ethical concerns and limit specific sampling for research studies. To overcome this problem, we used residual blood from routine clinical testing to monitor CD34⁺ cell counts in the first months of life. Our aim was to characterize the dynamics of circulating CD34⁺ cells and explore associations with prenatal and postnatal clinical events.

Methods: We retrieved residual blood samples from nine infants born <28 weeks gestational age (GA), collected from birth through eight postnatal weeks. CD34⁺ cell count was assessed using flow cytometry. The number of nucleated red and white blood cells, and hemoglobin concentration were also measured.

Results: Median (min-max) GA was 25+0 (22+3─27+5) weeks. CD34⁺ cell counts at birth ranged from 19 to 284 x 10⁶ cells/L. Between days 0 and 1, CD34⁺ cell count increased in four infants and decreased in four. By day 7, the proportion of CD34⁺ of total nucleated blood cells was significantly lower than at birth (p=0.018). High inter- and intra-individual variability in CD34⁺ cell count was observed. Notably, the highest CD34⁺ cell levels coincided with maternal or infant infections.

Conclusion: This pilot study demonstrates the feasibility of longitudinal monitoring of CD34⁺ hematopoietic stem and progenitor cells in extremely preterm infants using residual clinical blood samples. While limited by a small sample size, the study provides preliminary insights into early immune function and highlights directions for future research in larger cohorts.

Background: A major challenge after allogeneic haematopoietic stem cell transplantation for haematologic malignancies is the management of acute graft-versus-host disease (aGVHD), which remains associated with poor prognosis despite therapeutic advancements. We conducted a randomized, double-blinded, placebo-controlled Phase I/II clinical trial to assess the safety and efficacy of umbilical cord-derived mesenchymal stem cells (Cyto-MSC) as an upfront treatment in patients with grade II-IV aGVHD.

Methods: In this multicentre trial, 22 grade II-IV aGVHD patients were randomized to receive up to three infusions of Cyto-MSC (n = 14) or placebo (n = 8), alongside standard corticosteroid therapy. The primary endpoints were overall response (OR) at Day 28 and overall survival (OS) at 12 months. The secondary endpoints included correlation between responses at Day 28 with 12-month OS and exploratory analyses of immune cell subsets.

Results: No treatment-related adverse events were observed. There were no significant differences between Cyto-MSC and placebo in the OR at Day 28 and 12-month OS. Among patients with severe grade III-IV aGVHD who achieved OR by Day 28, those treated with Cyto-MSC had significantly improved 12-month OS compared to placebo (100% vs 50%, p=0.039). Furthermore, in patients with severe aGVHD and baseline CD4⁺ T_EMRA >35% or CD8⁺ T_EMRA >70%, the survival benefit was pronounced in the Cyto-MSC group (83.3% and 100%, respectively). In contrast, none of the placebo-treated patients with baseline CD4⁺ T_EMRA <35% (p=0.007) or CD8⁺ T_EMRA <70% (p=0.005) survived at 12 months. OS was significantly associated with OR at Day 28 (p<0.001), baseline CD4⁺ T_EMRA (p=0.004), and baseline CD8⁺ T_EMRA (p=0.004).

Conclusion: Patients with severe grade III-IV aGVHD, particularly those who respond early or have elevated baseline CD4⁺ T_EMRA (>35%) or CD8⁺ T_EMRA (>70%) levels, may have an overall survival advantage when treated with Cyto-MSC as an upfront therapy in combination with standard corticosteroids.